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BackgroundThe obligate intracellular protozoan Trypanosoma cruzi is the causative agent of Chagas disease, a neglected illness affecting millions of people in Latin America that recently entered non-endemic countries through immigration, as a consequence of globalization. The chemotherapy for this disease is based mainly on benznidazole and nifurtimox, which are very efficient nitroderivatives against the acute stage but present limited efficacy during the chronic phase. Our group has been studying the trypanocidal effects of naturally occurring quinones and their derivatives, and naphthoimidazoles derived from β-lapachone N1, N2 and N3 were the most active. To assess the molecular mechanisms of action of these compounds, we applied proteomic techniques to analyze treated bloodstream trypomastigotes, which are the clinically relevant stage of the parasite.Methodology/Principal FindingsThe approach consisted of quantification by 2D-DIGE followed by MALDI-TOF/TOF protein identification. A total of 61 differentially abundant protein spots were detected when comparing the control with each N1, N2 or N3 treatment, for 34 identified spots. Among the differentially abundant proteins were activated protein kinase C receptor, tubulin isoforms, asparagine synthetase, arginine kinase, elongation factor 2, enolase, guanine deaminase, heat shock proteins, hypothetical proteins, paraflagellar rod components, RAB GDP dissociation inhibitor, succinyl-CoA ligase, ATP synthase subunit B and methionine sulfoxide reductase.Conclusion/SignificanceOur results point to different modes of action for N1, N2 and N3, which indicate a great variety of metabolic pathways involved and allow for novel perspectives on the development of trypanocidal agents.

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Chagas disease (CD) is an infectious illness with great socioeconomic impact. Historically, it has mainly affected the poor population in Latin America. However, globalization sets a new scenario, featuring an increasing CD incidence worldwide especially due to parasite transmission by infected blood in non-endemic countries. Noteworthily, CD is predominantly marked by a subclinical progression, so that for most cases, the correct diagnosis may take years, even decades, post infection. Public actions such as active search of infected people and donors screening are imperative for both identification of individual health assistance and disease control. Nonetheless, the main affected areas lack in laboratory infrastructure, resource and specialized personnel, making the use of conventional immunoassays unfeasible. Moreover, parasite genetic variability and cross-reaction with close-related infectious diseases imposes a stringent diagnosis algorithm. Thus, although rapid tests are a great option, its applicability is still restricted in the context of this disease. In this regard, this chapter will discuss the use of immunochromatographic-based assays for CD, their limitations and perspectives. The performance of commercially available kits in comparison to the conventional serologic tests will be also debated, covering their antigen selection, origin of population studied and type of samples.